Multiple changes in cardiovascular (CV) reserve functions occurring over a lifetime limit the ability of older persons to maintain biological homeostasis as both CV and non-CV pathologies emerge. To determine CV reserve functions at entrance into study (EAge) and the rates at which these change over time in participants of the Baltimore Longitudinal Study of Aging (BLSA) who were free of clinical CV disease and ranged in age from 23 to 79. Design An initial and up to five serial radionuclide ventriculographs measurements over an average 10-year follow-up at seated rest and during upright cycle exercise to exhaustion of: cardiac output (CO), heart rate (HR), end diastolic and end systolic volumes (EDV and ESV), ejection fraction (EF). Longitudinal and cross-sectional data were analyzed using linear mixed-effects and multiple regression models. Peak exercise workload declined over time following EAge in all 84 male and 49 female subjects, as did peak exercise CO, HR, and EF; and peak ESV, SBP, and PP significantly increased. These rates of changes over time did not differ by EAge or gender. In contrast, peak EDV increased in some subjects, but decreased in others. The rate and direction of change in SV over time within individuals was directly correlated with the change in EDV. Rates at which peak SV and EDV changed over time had the largest impact on the rate at which peak CO declined. The between person variability of measured parameters at any EAge was nearly twice the variability that occurred over time within the same individuals. The rate at which peak CO, the most important cardiac reserve function, declines over time is dominated by the rates and direction of change in EDV and SV which differ among subjects. The within-person variability in changes that occur over time following EAge in most CV functions, however, is about 50% less than that measured between the same individuals at EAge. This suggests that relatively less time variant factors, eg. genetic, lifestyle, or environment, have a greater influence on CV reserve functions than do time-dependent changes (Aging). The impact of genetics, lifestyle, environment, and aging and interactions among these factors over time on CV reserve must be accounted for with respect to developing ideal CV disease prevention, detection, and management strategies for older patients.